Facts About DBA
Diamond Blackfan anemia (DBA) is a rare blood disorder that is also associated with birth defects or abnormal features. In DBA, the bone marrow (the center of the bone where blood cells are made) does not make enough red blood cells that carry oxygen throughout the body.
Signs and Symptoms
People with DBA have symptoms common to all other types of anemia, including pale skin, sleepiness, rapid heartbeat, and heart murmurs. In some cases, there are no obvious physical signs of DBA. However, about 30 to 47% of those with DBA have birth defects or abnormal features involving the face, head, and hands (especially the thumbs). They might also have heart, kidney, urinary tract, and genital organ defects. Many children are short for their age and might start puberty later than normal.
Diagnosis
It is usually diagnosed during the first year of life. Several tests can be used to tell if a person has DBA. One test a doctor can perform is called a bone marrow aspirate. This is a test in which a needle is inserted into a bone and a small amount of bone marrow fluid is taken out and studied under a microscope. Blood tests can also be done to see if there is a genetic basis for DBA or certain chemical abnormalities linked to DBA.
Treatment
To treat very low red blood cell counts in people with DBA the two most common options are corticosteroid medication and blood transfusions. Bone marrow/stem cell transplantation might also be considered. Some people need no specific therapy. A qualified doctor can recommend the best treatment options.
Causes and Risk Factors
Some people have a family history of the disorder. More than half of people with DBA have a known genetic cause. In many people with DBA, doctors do not know the cause.
If someone has DBA there is up to a 50% chance that each of his or her children will have DBA.
Who is Affected
DBA affects both boys and girls equally. It occurs in every racial and ethnic group. There are about 25 to 35 new cases of DBA each year in the United States and Canada.
Treatments
To treat very low red blood cell counts in people with Diamond Blackfan anemia (DBA) the two most common options are corticosteroid medication and blood transfusions. Bone marrow/stem cell transplant might also be considered. Some people need no specific therapy. A qualified doctor can recommend the best treatment options.
Corticosteroid Therapy (Prednisone, Prednisolone)
In Diamond Blackfan anemia (DBA), the bone marrow (the center of the bone where blood cells are made) does not make enough red blood cells. A special protein in red blood cells called hemoglobin carries oxygen to all of the organs in the body. When the number of red blood cells is low, the organs in the body do not get the oxygen they need.
Corticosteroids can help people with DBA make more red blood cells. They are powerful drugs used to treat many conditions. Corticosteroids are not the same type of drugs that athletes and other people take to increase muscle – those are called anabolic steroids.
This therapy is often one of the first types of treatments doctors recommend for people with DBA. Doctors do not know exactly why corticosteroids work, but about 80% of people with DBA who take them produce more red blood cells.
About Corticosteroid Therapy
The goal of corticosteroid therapy is to take only what the person needs to keep the hemoglobin (a protein in red blood cells that carries oxygen to all of the organs in the body) at a healthy level (about 10 g/dL).
Doctors usually prescribe a certain dose of corticosteroids for several weeks. If the hemoglobin in the body increases, then the dose may be decreased slowly. If the number of red blood cells drops too far, the dose might be increased. When the number of red blood cells is at a healthy level, the dose will be kept the same or slowly reduced.
Over time, the body might not respond to the corticosteroids and they will not work as well. If this happens, the doctor might increase the dose or suggest a different type of treatment such as blood transfusions or stem cell transplantation.
When changing the dose of corticosteroids, the doctor will check the amount of hemoglobin in the body using a blood test called a CBC (complete blood count) and reticulocyte count (this tells if the body is trying to make its own red blood cells).
If corticosteroids are going to work, the number of red blood cells usually increases in 2 to 4 weeks.
Side Effects
Corticosteroids have both short-term and long-term side effects. Low doses of corticosteroids may be helpful with minimal side effects, but use of high dose corticosteroids for a long time can cause serious side effects. People taking steroids must be watched carefully for side effects. Other treatments, such as red cell transfusions, should be considered if a patient requires high corticosteroid doses or if serious side effects develop.
Possible side effects of short-term corticosteroid use:
Upset stomach
Increased blood sugar
Increased hunger
Behavior changes, trouble sleeping, irritability
Increased risk of pneumonia, thrush (white coating in the mouth), and other infections
Weight gain, salt and water retention
High blood pressure
Increased fat on the face (rounded face), upper back, and belly
Stretch marks on the skin, acne, poor wound healing, increased and unusual hair growth
Possible side effects of long-term use (3 months or longer):
All short-term side effects
Poor growth in children (can be severe)
Brittle bones (bones break easily, problems with hips and shoulder joints)
Muscle weakness
Diabetes
Eye problems
Tips for Success
Take steroids exactly as prescribed by your doctor.
Take steroids in the morning (if prescribed once a day), and take them with food to prevent an upset stomach.
If you miss a dose of medicine, take it as soon as possible. If it is almost time for the next dose, skip the missed dose and return to the regular schedule. Do not take a double dose or extra doses.
Tell your doctor if you get sick. Your blood count might drop from the stress of being sick, and you might need extra doses of medicine or other treatment.
Always check with your doctor before changing the dose or stopping this medicine. It can be dangerous to stop corticosteroids suddenly. Your doctor may want to slowly reduce the amount you’re taking until you stop completely.
Talk with your doctor about any concerns. Make a list of your questions. Do your research so you can help make decisions about your treatment.
Blood Transfusion Therapy
About Blood Transfusion Therapy
In Diamond Blackfan anemia (DBA), the bone marrow (the center of the bone where blood cells are made) does not make enough red blood cells. A special protein in red blood cells called hemoglobin carries oxygen to all of the organs in the body. When the number of red blood cells is low, the organs in the body may not get the oxygen they need.
Blood transfusion is one way to increase the number of red blood cells. Blood transfusion means taking blood from a healthy person and giving it to someone else. Some people only need blood transfusions now and then, when the hemoglobin is too low. Other people need regular blood transfusions over a long period of time. This is called blood transfusion therapy.
In blood transfusion therapy the blood is given through a vein or a permanent intravenous (IV) device. Blood transfusions are usually given every 4–6 weeks in a treatment center, hospital, or outpatient transfusion center.
Some reasons that a person with DBA might receive regularly scheduled blood transfusions are:
Other treatments (such as corticosteroids) have been unsuccessful
Side effects of other treatments are not tolerated
Anemia is very severe or causes complications
Benefits
After a blood transfusion, many people feel better, have more energy, and are able to participate in more activities. Children who receive blood transfusion therapy may grow better than they did while on other therapy.
Side Effects and Risks
Negative side effects of blood transfusion therapy are uncommon but can include blood transfusion reactions, infections, the development of red blood cell antibodies, and iron overload in different organs of the body.
Blood transfusion reactions
Blood transfusion reactions are a problem caused by receiving blood. The most common problem is an allergic reaction. Allergic reactions may cause itching, hives or a rash, and rarely, may be associated with swelling, coughing, wheezing, and difficulty breathing. If these reactions occur, the doctor will recommend taking medicine before each transfusion.
Another potentially serious type of problem may occur up to 10 days after the transfusion. Call the doctor for the following: fever, rash, back pain, dark colored urine, or skin that is pale or has a yellow color to it (jaundice). These symptoms might suggest hemolysis, a form of rapid breakdown of the donated blood in the body called a “delayed transfusion reaction.”
Infections
A common concern about blood transfusion therapy is the risk of getting an infection from a blood transfusion. Blood centers make every effort to assure that the blood supply is safe. The blood center will not accept blood from anyone who does not meet all of the requirements for healthy blood donors.
In addition, the blood is thoroughly tested for all of the viruses and bacteria that we currently know can be passed from one person to another through blood. Vaccination will also help prevent certain infections like hepatitis A and B.
It is important to remember that the blood supply in the United States is very safe, so passing infections through blood transfusion is extremely rare.
Red blood cell antibodies
Everyone inherits certain red blood cell traits, just as we inherit eye color and hair color. If a person receives blood cells with traits that do not match their own, the body may reject the blood cells and make an “antibody” to them. This antibody would destroy any blood that the person receives in the future that contains the same trait.
Red blood cell antibodies can also cause a transfusion reaction and make it difficult for the blood center to find blood that will work. To prevent these antibodies from forming, the blood center identifies the special red blood cell traits in the person receiving blood and then finds donors that match it very closely.
Iron overload
Iron overload occurs following frequent blood transfusions. All red blood cells contain iron. The body uses as much iron as it needs, but it cannot get rid of the iron it does not need. The extra iron received during each blood transfusion is stored in organs such as the heart, liver, pancreas, and endocrine glands. Without treatment, this iron would continue to build up and eventually damage these organs. When receiving blood transfusion therapy, the person’s growth and development, iron levels, hormone levels, and the function of the body organs will be monitored very closely to help prevent serious damage. The doctor may recommend going to certain specialists to help monitor any damage. Anyone having blood transfusion therapy should not take vitamins or supplements that include iron because these also can increase the amount of iron stored in the body. It may be necessary to take medicine, called chelation drugs, to help remove excess iron from the body.
Stem Cell (Bone Marrow) Transplant
In Diamond Blackfan anemia (DBA), the bone marrow (the center of the bone where blood cells are made) does not make enough red blood cells. Red blood cells carry oxygen to all of the organs in the body. When the number of red blood cells is low, the organs in the body may not get the oxygen they need.
A stem cell transplant can help restore the marrow’s ability to make red blood cells, and it is currently the only known cure for DBA.
However, physical problems associated with DBA but not related to the bone marrow, such as a cleft palate or a heart defect, will not change. In addition, the person’s genes will still have DBA, so there is still a 50 percent chance of passing the disorder to any future children, if fertility is retained.
Stem cell transplant is an expensive and potentially dangerous procedure that can lead to death or severe chronic illness in some patients. For this reason, it typically is not a “first line” treatment. Other treatments, such as steroid medicine (corticosteroid) therapy and blood transfusion therapy, tend to be used first, if possible. Before deciding to have a transplant, people with DBA should discuss the pros and cons of this procedure with their medical team.
About Stem Cells
All of the blood cells in the body start out as immature cells called blood-forming stem cells. Stem cells are able to grow into other blood cells that mature and function as needed in the body. Stem cells create the three main types of blood cells: red blood cells that carry oxygen throughout the body, white blood cells that fight infection, and platelets that help the blood to clot and prevent abnormal bleeding.
Stem cells are located in three places—bone marrow (the spongy center of the bone where blood cells are made), peripheral blood (found in blood vessels throughout the body), and cord blood (found in the umbilical cord and collected after a baby’s birth). Stem cells for transplantation are obtained from any of these three places.
About Stem Cell Transplant
A stem cell transplant (also commonly referred to as a bone marrow transplant), takes healthy stem cells from a donor and gives them to the patient through a central line in a vein in the chest. The bag of stem cells usually looks similar to a bag of blood used for blood transfusion. This is because it contains red blood cells. The goal of a stem cell transplant is to replace unhealthy stem cells with new healthy ones. If all goes well, these healthy stem cells find their way to the bone marrow and begin to function and produce blood cells normally (called an engraft). It often takes several weeks for this to happen.
Stem Cell Donors
For a person to be a donor, the donated stem cells must closely match the patient’s Human Leukocyte Antigen (HLA) type. HLA markers are special proteins found on most cells in the body. The immune system uses these proteins — or markers — to recognize which cells belong in the body and which do not. These markers are inherited from both parents. Special tests called HLA typing or HLA tissue typing determines whether the patient and the donor cells match.
Close family members such as brothers and sisters (but rarely parents) are often used as donors because they are most likely to match the patient’s tissue type. Each sibling who has the same parents has a 25 percent chance of matching the patient’s tissue type. However, if a sibling also has one of the DBA genes, it will be passed to the recipient during the transplant. It is important to screen potential donors for DBA genes because there is a risk of transfer from a sibling who has the gene for DBA, but who has no symptoms.
If there is not a brother or sister or other family member who is a match for the patient, the transplant center can check the National Marrow Donor Program (NMDP) registry for an unrelated matching donor. In some instances, unrelated donors may be adequately matched and able to donate. However, the rate of successful transplant from matched unrelated donors (MUDs) is lower. The best scenario is an identically matched, sibling who does not have DBA.
The National Marrow Donor Program (NMDP) is a database containing the tissue types of more than six million potential volunteer donors. Visit the program online to learn more:http://www.marrow.org/index.html.
Benefits
For DBA patients, a stem cell transplant is intended to restore the marrow’s ability to make red blood cells. Once the body starts producing red blood cells, the patient may experience a decrease in signs and symptoms of anemia, such as tiredness and paleness. Often times, stem cell transplant may result in a cure of DBA and, when successful, may often extend a person’s life and improve the quality of life they are able to enjoy. The person will no longer require long-term steroid medicine or blood transfusions. The person’s blood type will actually change to that of the donor.
Risks
A stem cell transplant is a complex procedure with risks. Although some people with DBA experience few problems with transplant, others experience many problems and must endure frequent tests and hospitalizations. Before a stem cell transplant, the patient receives chemotherapy and occasionally radiation therapy to destroy their unhealthy stem cells. This is called a preparative regimen. Some side effects, such as nausea, vomiting, fatigue, loss of appetite, mouth sores, hair loss, and skin reactions may be due to the preparative regimen.
Several complications, some potentially fatal, can occur as a result of a stem cell transplant:
Infection
After the transplant, before the new marrow has started to grow, the number of white blood cells is low and the immune system (how the body fights infection and stays healthy) is very weak. During this time, the body is susceptible to infections, sometimes from the bacteria that live in the patient’s own body. Therefore, infections that normally would not be harmful can be very serious, and patients can die of them. Bacterial, viral, and fungal infections are often seen following transplant.
Graft-versus-host disease (GVHD)
Graft-versus-host disease (GVHD) occurs when the new stem cells (from the donor) do not recognize the patient’s cells and attacks them, leading to skin rashes, diarrhea, or liver abnormalities. GVHD can be acute or chronic and range in severity from mild to moderate to severe. Medicines are given to prevent GVHD. Mild and moderate GVHD can be treated successfully with drugs and does not increase the risk of the patient dying. The most severe degree of GVHD is less frequent, but very serious, and patients can die of this complication. A close match between the donor and recipient will reduce the risk for GVHD, thereby allowing a greater chance for the donor stem cells to produce normal blood cells without complications.
Transplant rejection (Graft Failure)
Graft failure happens when the patient’s immune system attacks the new stem cells from the donor. This happens because the patient’s immune system thinks the new cells are harmful and need to be destroyed. If the immune system wins the fight, the old stem cells will come back, along with the DBA.
Other risks
Some of the more common long-term risks of stem cell transplant include infertility (the inability to produce children) and cataracts (clouding of the lens of the eye, which can be fixed with surgery). Less common effects include long-term damage to organs such as the liver, kidneys, lungs, or heart, and the occurrence of cancers.
After Treatment
After the transplant regular check-ups are needed to identify and take care of any problems that may arise after a patient has a stem cell transplant. Initially, follow-up care involves clinic visits once or twice a week with platelet or blood transfusions, as needed. Long-term follow-up is necessary to maintain a healthy lifestyle, ensure that the DBA continues to be in remission, and ensure that any late effects of the transplant or DBA are caught early. During long-term follow up, growth and development, immunizations, fertility, and mental and physical health are monitored.
